Tec kinase Itk in gamma delta T cells is pivotal for controlling IgE production in vivo

In conventional alpha beta T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of the T cell receptor (TCR). Itk also regulates alpha beta T cell development, lineage commitment, and effector function. A well established feature of Itk super(-/-) mice is their inability to generate T helper type 2 (Th2) responses that produce IL-4, IL-5, and IL-13; yet these mice have spontaneously elevated levels of serum IgE and increased numbers of germinal center B cells. Here we show that the source of this phenotype is gamma delta T cells, as normal IgE levels are observed in Itk super(-/-)Tcrd super(-/-) mice. When stimulated through the gamma delta TCR, Itk super(-/-) gamma delta T cells produce high levels of Th2 cytokines, but diminished IFN gamma . In addition, activated Itk super(-/-) gamma delta T cells up-regulate costimulatory molecules important for B cell help, suggesting that they may directly promote B cell activation and Ig class switching. Furthermore, we find that gamma delta T cells numbers are increased in Itk super(-/-) mice, most notably the V gamma 1.1 super(+)V delta 6.3 super(+) subset that represents the dominant population of gamma delta NKT cells. Itk super(-/-) gamma delta NKT cells also have increased expression of PLZF, a transcription factor required for alpha beta NKT cells, indicating a common molecular program between alpha beta and gamma delta NKT cell lineages. Together, these data indicate that Itk signaling regulates gamma delta T cell lineage development and effector function and is required to control IgE production in vivo.